Immunohistochemical Expression of Ki-67 Antigen, Cox-2 and Bax/Bcl-2 in Prostate Cancer; Prognostic Value in Biopsies and Radical Prostatectomy Specimens
Introduction
Bcl-2 and Bax expressions have been proposed as prognostic factors in prostate cancer (PC) patients treated by radiotherapy as in surgical series [1], [2], [3] They have also been related to hormonal resistance [4]. Similarly, the tumour proliferative activity has also been validated as an excellent immunohistochemical (IHC) prognostic factor using Ki-67 (MIB-1) [5], [6], [7]. Recently, the expression of cycloxigenase-2 (Cox-2) has been studied in multiple tumours and PC. There is no consensus on its expression in PC, but it has been related to a more aggressive behaviour [8], [9], [10]. An agreement between researchers and clinicians is needed regarding Cox-2 patterns of expression in normal prostate, benign prostate hyperplasia (BPH), prostate intraepithelial neoplasia (PIN), PC and PC cell lines to justify the administration of Cox-2 inhibitors (i.e. Celecoxib) as prophylactic or therapeutic drugs in PC [11].
The aim of this work is to find out the prognostic value of the 4 mentioned molecules in the biopsy cores (C) of patients with PC, knowing their expression and reproducibility in C and surgical specimens (SP) after radical prostatectomy (RP). Other goals are to establish their relation with known clinico-pathological prognostic factors and among themselves.
Section snippets
Clinico-pathological data
Patients were selected between 1997 and 2001. Selection criteria were those cases with biopsies performed in our hospital not receiving neo or adjuvant hormonal treatment. Twenty-eight patients were excluded due to inadequate paraffined material for IHC techniques (mostly C samples). So, the study group was actually comprised of 91 patients (Table 1) operated by RP with sufficient C and SP paraffin-embedded material for researching purposes. The mean age of patients was 63.62 (range 45–74). We
Results
Our series had a median follow-up of 46,5 months (range 6–82). Sixty-two patients (68.1%) were free of disease, while 29 (31.9%) had progressed, 21 (72.4%) just as biochemical progression. Median time to biochemical progression was 12 ± 16.2 months (range 1–55 months). Seven patients (24.1%) had local or distant progression and one died due to tumour progression. Mean preoperative PSA was 12.57 ± 12.04 (range 1.3–64.7) ng/ml. Concordance between Gleason score in C and SP was statistically
Discussion
Expression of Bcl-2 in normal prostate glands is restricted to the basal cells and is never observed in secretory cells while Bax is expressed in basal and secretory cells. Bcl-2 has shown to be a negative prognostic factor in surgical series [1], [2] regardless of the Gleason score [14]. It has also proven its higher expression in RP performed at biochemical progression after radiotherapy [3]. Nevertheless, Brewster et al., having proven the prognostic value of Bcl-2 overexpression in SP,
Conclusions
Reproducibility of expression is high for Ki-67, Bcl-2 y Cox in biopsies, while Bax expression in biopsies tends to underscore its expression in radical prostatectomy specimens. These results should be validated by other researchers to establish interobserver variability. Bcl-2 expression is very low both in biopsies and surgical specimens. The IHC expression of Ki-67 and Cox-2 proteins in our study do offer valuable prognostic information, mostly Ki-67. We believe that expressions of both
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